• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1992년도 제1회 신약개발 연구발표회 초록집
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• pp.27-27
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• 1992

많은 홀몬, 성장인자 및 신경 전달물질들은 각각에 대한 세포막의 수용체와 결합하여 Phospholipase C (PLC)를 활성화시키므로서 신호를 세포내로 전달하여 세포의 성장, 대사, 신경 흥분, 수축 및 분비 등의 생리 현상을 나타내고 있다. 이 신호 전달의 중심 효소인 PLC는 현재까지의 효소 분리, 유전자 클로닝 등의 방법으로 3가지 Class에 적어도 8종유의 등위효소(Isozyme)들이 존재하고 있는 것으로 밝혀지고 있다. 본 연구에서는 이와 같은 등위효소에 특이적인 조절 물질을 선별할 수 있는 체계를 확립하기 위하여 새로운 동위효소의 분리 및 규명과 이 동위효소들에 대한 과발현 및 발현 세포주 개발을 추진하고 있다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.63-63
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• 1993

Phospoinositide-specific phospholipase C (PLC)는 세포막의 phosphoinositide를 분해하여 inositol phosphates와 diacylglycerol을 전달하는데 핵심적인 효소이다. PLC는 분자량과 1차구조의 비교에 의하여 type (PLC-$\beta$, ${\gamma}$, $\delta$)로 구분되며, 각 type마다 2-4종의 subtype이 존재하고 PLC isozyme들에 대한 현재가지의 각종 신호 전달 및 조절에 대한 연구를 종합하면: (1) PLC-$\beta$ type은 G-protein과 연결되어 신호를 전달받고, (2) PLC-${\gamma}$ type은growth factor receptor tyrosine kinase에 의하여 인산화 되어 활성화됨으로, 세포의 성장 신호를 전달하며. (3) PLC-$\delta$ type에 대한 신호 전달이나 조절은 밝혀지지 않고 있다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.68-88
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• 2002

Phospholipase A$_2$ (s) are esterases that hydrolyze the sn-2 ester bond in phospholipids, releasing a fatty acid and a lysophospholipid. We previously showed that most PLA$_2$ activity in rabbit renal proximal tubule cells (RPTC) was Ca$\^$2+/-independent, localized to the endoplasmic reticulum (ER-iPLA$_2$), and inhibited by the specific Ca$\^$2+/-independent PLA$_2$ inhibitor bromoenol lactone (BEL).(omitted)

• 생약학회지
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• 제38권3호통권150호
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• pp.277-280
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• 2007

In our continuing effort to investigate compounds having anti-inflammatory activity from natural products, Ailanthus altissima was examined. Among six compounds isolated from Ailanthus altissima, Luteolin-7-O-glucoside (L7G) along with ethanol extract of Ailnathus altissima (EAa) were chosen to determine their inhibitory activity on secretory recombinant phospholipase $A_2s$ enzyme activity in vitro. As a results, EAa inhibited human recombinant $sPLA_2-V$ ($IC_{50}$ of about 100 ${\mu}g/ml$) and $cPLA_2$, ($IC_{50}$ of about 59 ${\mu}g/ml$), while L7G showed strong inhibitory effect on $sPLA_2-A$, V and $cPLA_2$ with an $IC_{50}$ value of approximately 40 ${\mu}M$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.19-25
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• 1997

The C-terminus ends of the second putative transmembrane domains of both $M_1$ and $M_2$ muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T). This triplet is repeated as LYT-TYL in $M_1$ receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposedfashion (LYT-LYT) in the sequence of $M_2$ receptors. In our previous work, we investigated the possible significance of this unique sequence diversity for determining the distinct differential receptor function at the two receptor subtypes. However, we found mutation of the LYTTYL sequence of $M_1$ receptors to the corresponding $M_2$ receptor LYTLYT sequence demonstrated markedly enhanced the stimulation of phosphoinositide (PI) hydrolysis by carbachol without a change in its coupling to increased cyclic AMP formation. In this work, thus, the enhanced stimulation of PI hydrolysis in the LYTLYT $M_1$ receptor mutant was further investigated. The stimulation of PI hydrolysis by carbachol was enhanced in the mutant $M_1$ receptor, and this change was not due to alterations in the rate of receptor desensitization or sequestration. The observed larger response to carbachol at mutant $M_1$ receptors was also not due to an artifact resulting from selection of CHO cells which express higher levels of G-proteins or phospholipase C. Our data suggest that although the LYTTYL sequence in $M_1$ muscarinic receptors is not involved in determining receptor pharmacology, mutation of the sequence enhanced the coupling of $M_1$ receptors to the stimulation of phospholipase C.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.163-167
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• 2010

This study investigated the effects of the methanol extracts of Morinda citrifolia containing numerous anthraquinone and iridoid on phospholipase $A_2$ ($PLA_2$) isozyme. $PLA_2$ activity was measured using various $PLA_2$ substrates, including 10-pyrene phosphatidylcholine, 1-palmitoyl-2-[$^{14}C$]arachidonyl phosphatidylcholine ([$^{14}C$]AA-PC), and [$^3H$]arachidonic acid (AA). The methanol extracts suppressed melittin-induced [$_3H$]AA release in a concentration-dependent manner in RAW 264.7 cells, and inhibited $cPLA_2/sPLA_2$-induced hydrolysis of [$^{14}C$]AA-PC in a concentration- and time-dependent manner. A Dixon plot showed that the inhibition by methanol extracts on $cPLA_2$ and $sPLA_2$ appeared to be competitive with inhibition constants ($K_i$) of $3.7{\mu}g/ml$ and $12.6{\mu}g/ml$, respectively. These data suggest that methanol extracts of Morinda citrifolia inhibits both $Ca^{2+}$-dependent $PLA_2$ such as, $cPLA_2$ and $sPLA_2$. Therefore, Morinda citrifolia may possess anti-inflammatory activity secondary to $Ca^{2+}$-dependent $PLA_2$ inhibition.

• Journal of Microbiology and Biotechnology
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• 제12권1호
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• pp.71-76
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• 2002

Soil samples were screened for actinomycete strains capable of producing phospholipase D, and a strain, Streptomyces sp. YU100, showing a high transphosphatidylation activity was isolated. This strain secreted phospholipase D in a culture broth after 12 h of cultivation, and its productivity continued to increase for 36 h of fermentation. In addition, its transphosphatidylation rate of phosphatidylcholine to phosphatidylserine was almost $68\%$ within 1 h. The morphological and chemotaxonomical characteristics showed that this strain could be classified as a number of the Streptomycetaceae family, particularly due to the spiral form of its spore chain consisting of 60-70 smooth spores $(0.75{\times}1.0{\mu}m$) on an aerial mycelium, FA-2c type of fatty acid profile in the cell wall, and LL-DAP component in the cell wall peptidoglycan. A phylogenetic analysis of the 16S rDNA provided a clue that the strain YU100 was actually a member of the genus Streptomyces, because the determined sequence exhibited a higher homology with Streptomyes sp. ASB27, S. peucetius JCM9920, and S. griseus ATCC10137. A dendrogram based on the 16S rDNA sequences also showed a phylogenetic relationship between the strain YU100 and these strains. However, the strain YU100 has not yet been assigned to a particular species, because of absence of any other classified species with a high matching score.

• 한국응용곤충학회지
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• 제51권3호
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• pp.299-303
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• 2012

서양종 꿀벌 독의 채집시기와 지역에 따른 봉독의 성분 변화 및 약리효과에 미치는 영향을 검토하였다. 채집시기는 5월부터 9월까지, 채집지역은 전국 35개 지역으로부터 채취한 봉독을 대상으로 2010년과 2011년 2년에 걸쳐 동일 지역에서 동일한 방법으로 봉독을 채취하였다. 채취한 봉독은 액체크로마토그래피를 통해 멜리틴과 아파민 그리고 포스포리파아제 A2의 성분 함량을 분석하였다. 그 결과 채집시기와 지역에 따른 성분에 유의한 차이는 확인되지 않았다(One way-ANOVA, Duncan's test (${\alpha}$=0.05)). 봉독의 성분은 채집시기와 지역에 관계없이 멜리틴 $55.2{\pm}2.07%$, 아파민 $2.57{\pm}0.103%$ 그리고 포스포리파아제 A2는 $12.51{\pm}0.37%$을 차지하였다. 이상의 결과로부터 봉독은 채취시기에 따른 주요 성분은 차이를 갖고 있지 않았으며, 이는 꿀벌의 먹이, 사육온도 등 외부 환경이 봉독 분비에 영향을 주지 않는 것으로 사료되었다.

• 약학회지
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• 제59권4호
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• pp.158-163
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• 2015

Cardiac myocytes are subjected to fluid shear stress during each contraction and relaxation. Under pathological conditions, such as valve disease, heart failure or hypertension, shear stress in cardiac chamber increases due to high blood volume and pressure. The shear stress induces proarrhythmic longitudinal global $Ca^{2+}$ waves in atrial myocytes. In the present study, we further explored underlying cellular mechanism for the shear stress-induced longitudinal global $Ca^{2+}$ wave in isolated rat atrial myocytes. A shear stress of ${\sim}16dyn/cm^2$ was applied onto entire single myocyte using pressurized fluid puffing. Confocal $Ca^{2+}$ imaging was performed to measure local and global $Ca^{2+}$ signals. Shear stress elicited longitudinally propagating global $Ca^{2+}$ wave (${\sim}80{\mu}m/s$). The occurrence of shear stress-induced atrial $Ca^{2+}$ wave was eliminated by the inhibition of ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors ($IP_3Rs$). In addition, pretreatment of phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the generation of longitudinal $Ca^{2+}$ wave under shear stress. Our data suggest that shear-induced longitudinal $Ca^{2+}$ wave may be induced by $Ca^{2+}$-induced $Ca^{2+}$ release through the RyRs which is triggered by $PLC-IP_3R$ signaling in atrial myocytes.

• 한국미생물·생명공학회지
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• 제24권1호
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• pp.19-26
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• 1996

A phospholipase C (PLC) inhibitor (MT267-2B) was isolated from the culture broth of actinomycetes isolate MT2617-2 by the extraction with n-butanol and column chromatographic techniques. The molecular weight of the inhibitor was 1057, by the spectroscopic analyses of IR, $^{13}C$-and $^{1}H$-NMR and ESI-MS. The chemical structure of MT2617-2B was found to be a macrolide compound consisted of a hemiketal ring, polyhydroxyl and polymethyl groups, which had a malonate and guanidine group as its side chain. MT2617-2B produced its two isomers having the same molecular weight by standing in methanol solution at room temperature. Therefore, MT2617-2B was identified as copiamycin and niphithricin A, macrolide antibiotics. The values of $IC_{50}$ against PLC-${\gamma}$1 and PLC-${\beta}$1 were 25 and 50${\mu}$g/ml, respectively. MT2617-2B had antimicrobial activities against Staphylococcus aureus and Candida albicans, but not against Escherichia coli.